MDR1 – Multi-Drug Sensitivity

December 4, 2018

What is the MDR1 gene?

Multi-Drug Resistance 1 (MDR1) is a gene that is meant for helping to protect the brain. This gene specifically codes for P-glycoprotein, which is responsible for transporting certain drugs out of the brain. If this gene is mutated, it will create a defective protein, and consequently, drugs will remain and build up in the brain to toxic levels. This dominant gene is inherited from the parents, whether the parent has two copies of the gene or only one copy. If neither parent has a copy of the mutated MDR1 gene, then nor will the offspring.

What is the test for MDR1?

Through the Veterinary Clinical Pharmacology Laboratory in Washington State, dogs are able to be tested for the MDR1 gene with either a cheek swab or a blood sample. This can be completed either at home by ordering a kit from their website, or through your veterinarian. You will receive a copy of the results indicating if your dog is Normal/Normal, Normal/Mutant, or Mutant/Mutant. If your dog is Normal/Normal, then you don’t have to worry about any drugs related to the MDR1 gene. Dogs with even one copy of the MDR1 gene should be considered sensitive to the drugs indicated in this article.

What breeds are affected?

The most common breed associated with MDR1 mutation is the Collie, but generally, herding breeds are affected, and that includes any mixed breeds you might find at the shelter. Below is a list of breeds that are frequently affected by the MDR1 mutation.

Australian Shepherd

Border Collie

English Shepherd

Longhaired Whippet

McNab Shepherd

Old English Sheepdog

Shetland Sheepdog

Silken Windhound

Rough Collie

Smooth Collie

German Shepherd

American White Shepherd

English Shepherd

What drugs are not safe?

There are multiple drugs that will affect dogs with the mutated MDR1 gene. As long as your veterinarian is aware of your dog’s MDR1 status, they are able to consider which drugs are best suited for the current treatment. Those with a Normal/Mutant gene may be less susceptible to these drugs, though they would likely react to increased doses. Below is a list of drugs that should be generally avoided in dogs with an MDR1 status, or herding breeds or mixed breeds of unknown MDR1 status.

Ivermectin

Selamectin

Milbemycin

Moxidectin

Loperamide

Acepromazine

Butorphanol

Vincristine

Vinblastine

Doxorubicin

Paclitaxel

Apomorphine

The following list is drugs that are known to be removed from the brain via the MDR1 gene, but appear to be safely tolerated by dogs with the mutation.

Cyclosporin

Digoxin

Doxycycline

Morphine

Buprenorphine

Fentanyl

Ivermectin was a catalyst for the first testing of MDR1. The majority of farm dogs are herding breeds, and veterinarians used to give them high doses of injectable Ivermectin as a dewormer because they were highly susceptible to getting worms by being around livestock. With so many dogs showing adverse reactions, farmers and veterinarians looked for a pattern, which is where the adage ‘white feet, don’t treat’ came from.

Now, Ivermectin is still used as a dewormer in heartworm medication, and those that are sold in veterinary clinics have been tested as safe for dogs with the MDR1 mutated gene if used to the manufacturers’ specifications. There are other options for heartworm medication, so Ivermectin doesn’t necessarily need to be used. If your dog is still living near livestock, ensure they are not eating any feces or any discarded dewormer. When livestock are given dewormer, it is a high dose of Ivermectin, and it can remain in the feces (untested to know for how long) for your dog to accidentally ingest. High doses of Ivermectin are still used for treating mange and should be avoided in any MDR1 status dogs.

A common misconception is that MDR1 status dogs are affected by metronidazole, but that is inaccurate because it is not transported by P-glycoprotein. Also, vaccines do not cause any reactions related to the MDR1 gene. Any reactions to a vaccine are due to other reasons, such as allergy or the type of vaccine used.

What clinical signs should I watch for?

When there has been a buildup of toxins in the brain, your dog will start to show neurological symptoms, such as weakness, lethargy, ataxia, disorientation, tremors, seizures, blindness, and death. When any of these symptoms occur, call your veterinarian immediately. Certain drugs have reversal agents, but others don’t, and only supportive care can be given (IV fluids, nutritional support, and diligent monitoring). Recovery can take a long time due to the nature of the toxins remaining in the brain.

Seizures from the MDR1 mutation have no relation to epilepsy. Some herding breeds are prone to epilepsy, which is very different from seizures brought on by a buildup of toxins. It is possible for a dog to have both issues and an MDR1-induced seizure could trigger an epileptic seizure. An MDR1 seizure will always closely follow the administration of one of the drugs listed above.

What should I ask my breeder?

If you are looking to adopt one of the breeds listed above or a mixed breed that appears to have any mixture of the above breeds, see if the breeder has had the puppy or parents tested. A dog only needs to be tested once in its life as its DNA won’t change.

Breeders should give preference to breeding dogs with Normal/Normal MDR1 status, but simply removing all those that are not Normal/Normal would likely deplete the breeding stock too much. If there were not enough dogs to contribute to the gene pool then new genetic diseases or other health issues would become predominant, instead. Therefore, breeders should consider the mutation a fault like any other and weigh it against the other pros and cons of breeding any particular dog.

If your breeder has completed the testing on either the puppy or the parents, please be sure you have a copy of the results to give to your veterinarian so they can be treated appropriately. If the puppy has been purchased for breeding, MDR1 testing should be considered as important as any other test for that breed.

Discussing MDR1 with your veterinarian.

Any veterinary clinic that you bring your dog to ensure the veterinarian knows its MDR1 status. Your veterinarian is the one who should know which drugs are safe and which are not so that they can make an appropriate plan whenever your dog needs treatment. Their status can also be taken into account if any neurological signs appear so that the veterinarian can give a correct diagnosis.

If you don’t yet know the MDR1 status of your dog, your veterinarian can also help with the testing. If you go through a veterinary clinic to do the testing, the results will always be in their file. Your veterinarian will be happy to answer any further questions you might have that weren’t answered in this article.